In this application, I propose to work on sensing and understanding innate immunity in ischemic heart disease. I will ask the overarching question how cardiovascular disease, and more specifically the risk factor hypertension, affects hematopoiesis, i.e. innate immune cell production, in the bone marrow. I propose to tackle two major goals: 1. to develop and validate fundamental science and translational imaging tools that provide in vivo data on bone marrow hematopoiesis, including intravital microscopy and positron emission tomography/magnetic resonance imaging; 2. to decipher how ischemic heart disease disease alters bone marrow function, and the organ's output of inflammatory immune cells. My immediate focus will be the bone marrow vasculature. This focus is motivated by the influence of the vascular stem cell niche, which instructs hematopoietic stem cell proliferation, progenitor lineage bias and leukocyte migration. At the same time, the bone marrow vasculature is part of the systemic circulation, and therefore exposed to cardiovascular risk and disease-promoting pathways. It is unknown if and how bone marrow vasculature changes in ischemic heart disease, and how these changes modulate systemic innate immune cell supply. Motivated by evidence that systemic leukocyte levels correlate with cardiovascular mortality, I will address this knowledge gap with the ultimate goal to discover new therapeutic targets for patients with atherosclerosis.

Public Health Relevance

I propose to work on sensing and understanding innate immunity in ischemic heart disease. I will ask the overarching question how cardiovascular disease, and more specifically the risk factor hypertension, affects innate immune cell production in the bone marrow.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Unknown (R35)
Project #
1R35HL139598-01
Application #
9428723
Study Section
Special Emphasis Panel (ZHL1)
Program Officer
Danthi, Narasimhan
Project Start
2018-02-01
Project End
2025-01-31
Budget Start
2018-02-01
Budget End
2019-01-31
Support Year
1
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02114